Previously, we had developed a fluorescence-guided angioplasty system utilizing fluorescence spectroscopy to direct a pulse dye laser for selective atheroma removal. However, this device was limited in clinical application because the delivery system comprised a single small diameter laser fiber wire which resulted in primary channel recanalization but required subsequent balloon angioplasty for definitive luminal expansion in all cases. Therefore, it became necessary to develop a larger catheter-based system which would provide definitive atheroma removal with large surface area recanalization of stenotic or occluded coronary and peripheral vessels. Concentric and eccentric multifiber design catheters with a working through lumen for guide-wire placement were tested to asses fluorescence spectroscopic sensing and tissue ablation parameters. These catheters were 4.5 French for coronary use and 6.5 French for peripheral artery use. Trackability and flexibility were compatible with easy in vivo transcatheter application. After extensive in vitro testing utilizing human ecropsy atherosclerotic material, we concluded that a multifiber fluorescence-sensing laser catheter still provides reliable tissue recognition and accurately guides plaque ablation by a 480 nM pulse dye laser. Parameter studied included changes in computer algorithms for composite sensing of heterogeneous sites, photobleaching phenomena, florescence changes associated with thermal tissue effects, and requirements to elicit a homogeneous large area crater from multiple small fibers. These basic evaluations have provided the impetus for several design changes which we expect will result in a working catheter design for clinical studies in the near future.